rs1688075

Variant names:

• chr2-113100619-C-A
• rs1688075
• ENST00000409052.6:n.-472+1030C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000409052.6(IL1RN):​n.-472+1030C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 152,240 control chromosomes in the GnomAD database, including 63,125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (63125 hom., cov: 33)
• Consequence: IL1RN ENST00000409052.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 7 publications found

Genes affected

IL1RN (HGNC:6000): (interleukin 1 receptor antagonist) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses, particularly in the acute phase of infection and inflammation. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

IL1RN Gene-Disease associations (from GenCC):

• sterile multifocal osteomyelitis with periostitis and pustulosis

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-472+1030C>A		intron_variant	Intron 1 of 8		XP_011509423.1
IL1RN	XM_047444184.1	c.-644+1030C>A		intron_variant	Intron 1 of 9		XP_047300140.1
IL1RN	XM_047444185.1	c.-601+1030C>A		intron_variant	Intron 1 of 9		XP_047300141.1
IL1RN	XM_047444186.1	c.-409+1030C>A		intron_variant	Intron 1 of 7		XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	n.-472+1030C>A		intron_variant	Intron 1 of 9	5		ENSP00000387210.1
IL1RN	ENST00000463073.6	n.103+1030C>A		intron_variant	Intron 1 of 3	5
IL1RN	ENST00000465812.6	n.275+1030C>A		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137902 AN: 152122 Hom.: 63077 Cov.: 33

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.888

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.907 AC: 138014 AN: 152240 Hom.: 63125 Cov.: 33 AF XY: 0.900 AC XY: 67010 AN XY: 74438

African (AFR) AF: 0.943 AC: 39200 AN: 41558

American (AMR) AF: 0.876 AC: 13399 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2998 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2441 AN: 5154

South Asian (SAS) AF: 0.855 AC: 4124 AN: 4822

European-Finnish (FIN) AF: 0.903 AC: 9577 AN: 10606

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63272 AN: 68024

Other (OTH) AF: 0.889 AC: 1875 AN: 2110

Alfa AF: 0.929 Hom.: 8494

Bravo AF: 0.902

Asia WGS AF: 0.712 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.70
PhyloP100		-0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1688075; hg19: chr2-113858196;